Hypoxia Inducible Factor 1-Alpha (HIF-1 Alpha) Is Induced during Reperfusion after Renal Ischemia and Is Critical for Proximal Tubule Cell Survival

Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

The BCG Moreau Vaccine Upregulates In Vitro the Expression of TLR4, B7-1, Dectin-1 and EP2 on Human Monocytes

Background: Tuberculosis (TB) is currently the second greatest killer worldwide and is caused by a single infectious agent. Since Bacillus Calmette–Guérin (BCG) is the only vaccine currently in use against TB, studies addressing the protective role of BCG in the context of inducible surface biomarkers are urgently required for TB control. Methods: In this study, groups of HIV-negative adult healthy donors (HD; n = 22) and neonate samples (UCB; n = 48) were voluntarily enrolled. The BCG Moreau strain was used for the in vitro mononuclear cell infections. Subsequently, phenotyping tools were used for surface biomarker detection. Monocytes were assayed for TLR4, B7-1, Dectin-1, EP2, and TIM-3 expression levels. Results: At 48 h, the BCG Moreau induced the highest TLR4, B7-1, and Dectin-1 levels in the HD group only (p-value p-value p-value < 0.05). Conclusions: This study uncovers critical roles for biomarkers after the instruction of host monocyte activation patterns. Understanding the regulation of human innate immune responses is critical for vaccine development and for treating infectious diseases

Meta-analytic modeling of the decline in performance of fungicides for managing soybean rust after a decade of use in Brazil

An apparent decline of fungicide performance for the control of soybean rust in Brazil has been reported but the rate at which it has occurred has not been formally quantified. Control efficacy and yield response to three fungicides applied as single active ingredients (a.i.)—azoxystrobin (AZOX), cyproconazole (CYPR), and tebuconazole (TEBU)—and four applied as mixtures—AZOX+CYPR, picoxystrobin + CYPR, pyraclostrobin + epoxiconazole, and trifloxystrobin + prothioconazole (TRIF+PROT)—were summarized using network meta-analytic models fitted to mean severity and yield data from 250 trials (10-year period). The effect of year was tested on both variables in a meta-regression model. Overall control efficacy ranged from 56 to 84%; the three single-a.i. fungicides performed the poorest (56 to 62%). Yield increase for single-a.i. fungicides was as low as 30% but ranged from 47 to 65% for the premixes. Significant declines in both variables were detected for all fungicides except TRIF+PROT. For TEBU, control efficacy (yield response) declined the most: 78% (18%) to 54% (8%) from 2004–05 to 2013–14. The recent surge of resistant populations of Phakopsora pachyrhizi to both demethylation inhibitor and quinone outside inhibitor fungicides is likely the driving force behind a significant decline after 4 years of fungicide use

"O caminho se faz ao caminhar": processo de reativação de conselhos locais de saúde em Sobral, a partir do protagonismo cidadão "A path is made by walking": reactivation process of local health councils in Sobral through citizens' leadership

O presente artigo tem como objetivo descrever o processo de formação política de lideranças populares com vistas à reativação dos Conselhos Locais de Desenvolvimento Social e Saúde (CLDSS) no município de Sobral - CE. Os 48 mobilizadores locais, como foram denominados, obtiveram formação de 40h/aula intensas com metodologia dialógica, avaliada e planejada após cada oficina para contemplar as necessidades apontadas pelo grupo. Também foi desenvolvido acompanhamento das ações em território visando apoio técnico e pedagógico. . Entre os resultados obtidos ressaltamos: expansão de 5(cinco) para 20 (Vinte) CLDSS; maior envolvimento entre Conselheiros municipais e equipe de saúde, assim como maior apoio aos CLDSS nos diversos bairros e distritos;, maior divulgação das ações do CLDSS em rádios comunitárias e espaços diversificados de encontros, por exemplo em praças públicas.<br>This article presents the process of political formation of popular leaders with the objective of reactivating the Local Councils and Health (CLS) in the municipality of Sobral, state of Ceará, Brazil. The 48 local popular leaders received a 40 hours intensive training, based on dialogical methodology; assessment of the workshops was made after each one of them, in order to adapt the planning to the needs identified by the group. Follow up actions in their territory were also developed, for technical and pedagogical back up. Some of the results achieved were the expansion of the number of CLSs, from five to twenty; greater engagement and better understanding between Municipal councilors and the local health teams; finally, greater support from the population to the CLDSS in many neighborhoods and districts, wider dissemination of information about CLDSS actions in community radios and various meeting spaces, for example in public squares